1. Field of the Invention.
This invention relates generally to bovine erythrocyte preparations. In particular, the present invention relates to methods of using bovine erythrocyte preparations for treating, preventing, or inhibiting enterotoxigenic Escherichia coli infections.
2. Description of the Related Art.
Diarrhea caused by enterotoxigenic Escherichia coli (ETEC), commonly referred to as travelers' diarrhea, is a common health problem among travelers visiting less developed or tropical countries. See Peltola, H., et al. (1991) Lancet 338:1285-1289 and Ericsson, C. D. et al. (1993) Clin. Infect. Dis. 16:616-626. Diarrhea caused by ETEC and other ETEC infections are important concerns for military personnel when deployed to less developed countries. See Wolf, M. K., et al. (1993) Clin. Microbiol. 31:851-856 and Bourgeois, A. L., et al. (1993) Am. J. Trop. Med. Hyg. 48:243-248. ETEC maybe transmitted by food or water contaminated with animal or human feces. ETEC produces two toxins, a heat-stable toxin (ST) and a heat-labile toxin (LT). ETEC infections may cause profuse watery diarrhea, abdominal cramping, fever, nausea, vomiting, chills, loss of appetite, headache, muscle aches, and bloating.
The current therapy for travelers' diarrhea is to initiate treatment with agents such as bismuth subsalicylate (Pepto-Bismol®), antidiarrheals such as diphenoxylate with atropine (Lomotil®), loperamide HCl (Immodium®), attapulgite (Kaopectate®) and the like, rehydration therapy, and combinations thereof. The majority of the treatments involve the non-specific removal of the offending agents (i.e. toxins) from the intestinal tract. Only in moderate to severe cases of diarrhea where distressing or incapacitating symptoms are reported is antimicrobial therapy recommended. ETEC is frequently resistant to common antibiotics such as trimethoprim-sulfamethoxazole and ampicillin. Fluoroquinolones such as ciprofloxacin have shown some efficacy. Antibiotics are not usually effective at reducing clinical symptoms of the disease and problems associated with antibiotic resistance can occur. Prophylactic use of antibiotics is not recommended. Thus, therapies that specifically remove ETEC from the intestine are needed to provide more effective treatments for ETEC diarrhea.
In order to initiate the infectious process of diarrhea, ETEC must adhere to the host intestinal epithelial cells via the binding between bacterial adhesins and host receptors. This binding is commonly referred to as adhesion-receptor interaction. See Beachey, E. H. (1981) J. Infect. Dis. 143:325-345; Satterwhite, T. K., et al. (1978) Lancet. 2:181-184; and Warner, L. and Y. S. Kim. (1989) “Intestinal Receptors for Microbial Attachment”, Eds. M. J. G. Farthing, and G. T. Kensch, ENTERIC INFECTION: MECHANISMS, MANIFESTATIONS AND MANAGEMENT, pp. 31-40. Raven Press, N.Y. One treatment method that is based on this adhesin-receptor interaction, described by U.S. Pat. No. 5,897,860 ('860 patent), involves an oligosaccharide covalently attached to a solid support, wherein the oligosaccharide binds E. coli heat-labile toxin. The '860 patent does not prevent or treat ETEC infections as the methods merely immobilize or neutralize the heat-labile toxin (LT). Thus, the enterotoxigenic E. coli are still capable of adhering to the intestinal epithelial cells, colonizing and producing more LT.
Thus, a need still exists for a method for treating, preventing, or inhibiting ETEC infections, diseases, or disorders such as travelers' diarrhea.